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dc.contributor.authorGomez-Herreros, F-
dc.contributor.authorZagnoli-Vieira, G-
dc.contributor.authorNtai, I-
dc.contributor.authorMartínez Macías, M-
dc.contributor.authorHerrero-Ruíz, A-
dc.contributor.authorAnderson, RM-
dc.contributor.authorCaldecott, K-
dc.identifier.citationNature Communications, 8, 2017en_US
dc.description.abstractDNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation ‘hotspot’, MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability.en_US
dc.titleTDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcriptionen_US
dc.relation.isPartOfNature Communications-
Appears in Collections:Dept of Life Sciences Research Papers

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